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Tree-based scan statistics to generate drug repurposing hypotheses: a test case using sodium-glucose cotransporter-2 inhibitors.
Tan, George S Q; Maro, Judith C; Wang, Shirley V; Toh, Sengwee; Morton, Jedidiah I; Ilomäki, Jenni; Wong, Jenna; Li, Xiaojuan.
Afiliación
  • Tan GSQ; Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Australia.
  • Maro JC; Baker Heart and Diabetes Institute, Melbourne, Australia.
  • Wang SV; Department of Population Medicine, Harvard Medical School & Harvard Pilgrim Health Care Institute, Boston, MA, USA.
  • Toh S; Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Morton JI; Department of Population Medicine, Harvard Medical School & Harvard Pilgrim Health Care Institute, Boston, MA, USA.
  • Ilomäki J; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Wong J; Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Australia.
  • Li X; Baker Heart and Diabetes Institute, Melbourne, Australia.
Am J Epidemiol ; 2024 Sep 11.
Article en En | MEDLINE | ID: mdl-39270669
ABSTRACT
Most drug repurposing studies using real-world data focused on validating, instead of generating, hypotheses. We used tree-based scan statistics to generate repurposing hypotheses for sodium-glucose cotransporter-2 inhibitors (SGLT2i). We used an active-comparator, new-user design to create a 11 propensity-score matched cohort of SGLT2i and dipeptidyl peptidase-4 inhibitors (DPP4i) initiators in the MerativeTM MarketScan® Research Databases. Tree-based scan statistics were estimated across an ICD-10-CM-based hierarchical outcome tree using incident outcomes identified from hospital and outpatient diagnoses. We used an adjusted P≤0.01 as the threshold for statistical alert to prioritize associations for evaluation as repurposing signals. We varied the analyses by tree size, scanning level, and clinical settings for outcomes. There were 80,510 matched SGLT2i-DPP4i initiator pairs with 215,333 outcomes among SGLT2i initiators and 223,428 outcomes among DPP4i initiators. There were 18 prioritized associations, which included chronic kidney disease (P=0.0001), an expected signal, and anemia (P=0.0001). Heart failure (P=0.0167), another expected signal, was identified slightly beyond the statistical alert threshold. Narrowing the outcome tree, scanning at different tree levels, and including outcomes from different clinical settings influenced the scan statistics. We identified signals aligning with recently approved indications of SGLT2i, plus potential repurposing signals supported by existing evidence but requiring future validation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Am J Epidemiol Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Am J Epidemiol Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos